Under specific circumstances, skin cells can change their differentiated state from a skin to a neuronal state. This is observed in several systems, from worms to flies to vertebrates. For example, in the second larval stage of the nematode C.elegans, the differentiated skin cell V5 generates a neuroblast that then produces two mechanoreceptor neurons. The goal of my research proposal is to make use of the amenability of C.elegans to forward genetic screens to identify genes that are required in this skin-to-neuron transformation. I have already established a collection of these types of mutants and have identified a subset of them as phylogenetically conserved transcription factors that may have similar roles in vertebrates. In Specific Aim #1, I propose to classify the mutants according to phenotype. In Specific Aim #2, I propose to determine the molecular identity of these mutants and to carry out a preliminary analysis of their function through genetic pathway analysis. Based on the previous proof-of- principle identification of a phylogenetically and functionally conserved transcription factor (lin-32 in C.elegans and its ortholog Atoh1 in mouse), I expect to reveal genes whose vertebrate homologs may have similar functions in skin- to-neuron transitions and that may help us better understand this fascinating biological process. PUBLIC HEALTH RELEVANCE: Under specific circumstances, skin cells can change their differentiated state from a skin to a neuronal state. This is observed in several systems, from worms to flies to vertebrates. Based on the previous proof-of-principle identification of a phylogenetically and functionally conserved transcription factor (lin-32 in C.elegans and its ortholog Atoh1 in mouse), I expect to reveal genes whose vertebrate homologs may have similar functions in skin-to-neuron transitions and that may help us better understand this fascinating biological process!